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O Ramon

Publications and source records attributed to O Ramon.

5 recordsLinked to original sources
PubMed2001

2'-deoxyguanosine oxidation is associated with decrease in the DNA-binding activity of the transcription factor Sp1 in liver and kidney from diabetic and insulin-resistant rats.

Over the years, several lines of evidence have emerged supporting the role of oxidative stress in the development of diabetic complications. This could involve the increase in the production of reactive oxygen species and the decrease in antioxidative defense systems. Modulation of the level of intracellular reactive oxygen species is likely to affect the intracellular redox homeostasis, which is crucial for numerous biological events such as the transcriptional activation of genes. In this work we studied the binding of the redox transcription factors Sp1 and NF-kappaB extracted from kidney and liver of streptozotocin diabetic (STZ) and fructose-fed rats using electrophoretic mobility shift (EMSA) assay. In addition, the level in 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) was assessed within DNA by high performance liquid chromatography with electrochemical detection (HPLC-EC). A decrease in the affinity of Sp1 to DNA was observed in the kidney of STZ rats and fructose-fed rats (15% +/- 8.3 and 54% +/- 6.9, respectively, versus control group set to 100%). This was also found to occur to a lower extent, in the liver. Interestingly, higher levels of 8-oxodGuo, a biomarker of DNA oxidation, were measured in the kidney of diabetic rats. Therefore, the modification in the binding efficiency of Sp1 or NF-kappaB could be related to reactive oxygen species-mediated DNA damage.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2001

[Glucose and redox sensitive transcription factors: consequences on the insulin receptor].

During diabetes an oxidizing stress can be observed, whose origins are multiple. This stress can be regarded as a particular messenger, certainly modifying the transduction of the insulinic signal but also the activity of certain transcription factors. Indeed NF-kappa B activity is increased, while Sp1 activity drops in this context. NF-kappa B activation takes certainly part in vascular remodeling and plays a role in the genesis of the oxidative stress. Hence, NF-kappa B activity precociously increases in the states of insulin resistance before hyperglycemia sets in. Sp1 undergoes a significant fall in activity in the presence of glucose. This activity can be restored by antioxydants in the cell culture medium, Sp1 being necessary to insulin receptor expression, the question arises whether this drop in activity modifies significantly the insulin expression.

Arteriosclerosis↗
PubMed1999

Effects of 8-oxo-7,8-dihydro-2'-deoxyguanosine on the binding of the transcription factor Sp1 to its cognate target DNA sequence (GC box).

Emphasis was placed in this work on the assessment of the role of guanine bases in the interaction of transcription factor SP1 with its cognate DNA sequence. For this purpose, each guanine residue of the 5'-GGGGCG-GGG-3' (GC box) target DNA sequence was substituted in turn by 8-oxo-7,8-dihydro-2'-deoxyguanosine. The latter oxidized nucleotide which is likely to be present in mammalian DNA and exhibit mutogenic features is expected to be involved in age-related diseases and cancer. The effect of the incorporation of 8-oxodGuo into DNA on the binding of transcription factor Sp1 was studied using electrophoretic mobility shift assays with nuclear extracts from HeLa cells. When guanines at position G '2, G '3, G '4, G '5 and G'6 were replaced with 8-oxodGuo, binding of Sp1 was only 28%, 30%, 7%, 5% and 21%, respectively, to that of the non-substituted oligonucleotide. The binding is less affected when guanines at position G'1, G'7, G'8 and G'9 were substituted by 8-oxodGuo. Results show up the importance of the core of the GC box and the stronger contribution of the second and the third zinc finger to the binding with DNA. All together, this suggests that incorporation of 8-oxodGuo may alter the expression of the gene regulated by Sp1 and affect the response of the cell.

8-Hydroxy-2'-Deoxyguanosine↗